Bacterial pathogens are responsible for variety of diseases worldwide. Among these pathogens are Haemophilus influenza type a (“Hia”), Haemophilus influenza type b (“Hib”), Staphylococcus aureus (“S. aureus”) and Staphylococcus epidermidis (“S. epidermidis”). H. influenza type a has been reported to cause infections in Africa (Wall et al. (1986), Bull World Health Organ 64, 553-8; Wall et al. (1985), Lancet 845) and other countries (Rutherford et al. (1984), Ped Inf Dis 3, 575-77). Haemophilus influenza type b causes serious diseases, including mental retardation, which have the highest incidence in infancy and childhood. Staphylococcus aureus causes several diseases, the most frequent and serious of which are bacteremia and its complications in hospitalized patients. In particular, S. aureus can cause wound infections and infections associated with catheters and prosthetic devices. Serious infections associated with S. aureus bacteremia include osteomyelitis, invasive endocarditis and septicemia. Staphylococcus epidermidis causes disease primarily in patients with impaired host defenses or altered microbial flora, and is common in newborns. In particular, S. epidermidis can cause urinary tract infections, infections associated with IV catheters, meningitis in patients with subacute bacterial endocarditis, and it can cause mastitis in dairy animals.
Bacillus pumilus strain Sh 18 (“B. pumilus Sh18”) is a nonpathogenic, enteric, gram-positive bacterium. It has been reported that this bacterium produces a cell wall polysaccharide (sometimes referred to as a teichoic acid) that cross-reacts serologically with the capsular polysaccharide (CP) of Hib (Argman et al. (1974), J Immunol. 112, 649-55). This cross reactivity has been attributed to poly(ribotol phosphate) known to be present in cell wall associated teichoic acids of at least some bacilli (Kojima et al. (1985) J. Bacteriol 161, 299-306). No cross-reactivity, however, was observed with Hia CP, which is structurally similar to Hib CP, and which also contains ribotol phosphate in its subunit. It has been suggested that enteric, non-pathogenic gram positive bacteria, such as B. pumilus Sh18, may serve as a source of natural immunity against Hib in children over 6 years old and in adults (Bradshaw et al. (1971), Lancet 1095-6). Cross reactivity of B. pumilus Sh18 cell wall polysaccharide (CWP) with bacterial cell surface polysaccharides other than Hib has not been suggested or reported previously.
One aspect of the present invention is a vaccine comprising a glycoconjugate preparation containing polysaccharides from the B. pumilus Sh18 cell wall. This vaccine, surprisingly, cross reacts with surface polysaccharide material from all four of the pathogenic bacteria discussed above.